2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Aphasia

Alzheimer's disease is the most common form of dementia accounting for 50-60% of all dementia cases. This chapter briefly reviews the history of Alzheimer's disease and provides an overview of the clinical syndromes associated with Alzheimer pathology and their associated neuroimaging findings. This chapter also reviews the neuropathology and genetics of Alzheimer's disease and concludes by discussing current work undertaken to identify suitable in vivo biomarkers for the disease.

Topics: Adaptor Proteins, Signal Transducing; Alzheimer Disease; Amyloid beta-Protein Precursor; Aniline Compounds; Aphasia; Apolipoprotein E4; ATP-Binding Cassette Transporters; Atrophy; Brain; Cognition; HLA Antigens; Humans; Magnetic Resonance Imaging; Memory; Neuroimaging; Nuclear Proteins; Positron-Emission Tomography; Presenilins; Receptors, Complement 3b; Thiazoles; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Tumor Suppressor Proteins

Apraxia of speech is a motor speech disorder characterized by combinations of slow speaking rate, abnormal prosody, distorted sound substitutions, and trial-and-error articulatory movements. Apraxia of speech is due to abnormal planning and/or programming of speech production. It is referred to as primary progressive apraxia of speech (PPAOS) when it is the only symptom of a neurodegenerative condition. Past reports suggest an association of PPAOS with primary 4-repeat (4R) tau (e.g., progressive supranuclear palsy, corticobasal degeneration), rather than amyloid, pathology. The goal of the current study was to investigate the distribution of tau tracer uptake using [18F]AV-1451 positron emission tomography (PET) imaging in patients with PPAOS. Fourteen PPAOS patients underwent [18F]AV-1451 PET (tau-PET) imaging, [C11] Pittsburgh Compound B (PiB) PET and structural MRI and were matched 3:1 by age and sex to 42 cognitively normal controls. Tau-PET uptake was assessed at the region-of-interest (ROI) level and at the voxel-level. The PPAOS group (n = 14) showed increased tau-PET uptake in the precentral gyrus, supplementary motor area and Broca's area compared to controls. To examine whether tau deposition in Broca's area was related to the presence of aphasia, we examined a subgroup of the PPAOS patients who had predominant apraxia of speech, with concomitant aphasia (PPAOSa; n = 7). The PPAOSa patients showed tau-PET uptake in the same regions as the whole group. However, the remaining seven patients who did not have aphasia showed uptake only in superior premotor and precentral cortices, with no uptake observed in Broca's area. This cross-sectional study demonstrates that elevated tau tracer uptake is observed using [18F]AV-1451 in PPAOS. Further, it appears that [18F]AV-1451 is sensitive to the regional distribution of tau deposition in different stages of PPAOS, given the relationship between tau signal in Broca's area and the presence of aphasia.

Topics: Aged; Aged, 80 and over; Amyloid; Aniline Compounds; Aphasia; Apraxias; Brain; Broca Area; Carbolines; Case-Control Studies; Contrast Media; Cross-Sectional Studies; Disease Progression; Female; Frontal Lobe; Humans; Male; Middle Aged; Motor Cortex; Positron-Emission Tomography; tau Proteins; Thiazoles

A subset of patients with Alzheimer's disease (AD) present with early and prominent language deficits. It is unclear whether the burden of underlying β-amyloid pathology is associated with language or general cognitive impairment in these subjects.. The relationship between cortical β-amyloid burden on [(11) C]Pittsburgh compound B (PiB) positron emission tomography (PET) and performance on the Montreal Cognitive Assessment (MoCA), the Wechsler Memory Scale - Third Edition (WMS-III), the Boston Naming Test (BNT) and the Western Aphasia Battery (WAB) was assessed using regression and correlation analyses in subjects presenting with aphasia who showed β-amyloid deposition on PiB PET.. The global PiB ratio was inversely correlated with MoCA (P = 0.02) and the WMS-III Visual Reproduction (VR) subtest (VR I, P = 0.02; VR II, P = 0.04). However, the correlations between PiB ratio, BNT (P = 0.13), WAB aphasia quotient (P = 0.11) and WAB repetition scores (P = 0.34) were not significant.. This study demonstrates that an increased cortical β-amyloid burden is associated with cognitive impairment, but not language deficits, in AD subjects presenting with aphasia. The results suggest that β-amyloid deposition could be partly contributing to impaired cognition in such patients whilst language dysfunction may be more influenced by other pathological mechanisms, perhaps downstream pathways of β-amyloid deposition.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Aphasia; Cerebral Cortex; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Thiazoles